Thursday, November 11, 1999 Published at 06:18 GMTHealthScientists herald anti-depressant progressUS research could herald new avenues for treatment of depressionAnti-depressants may control mood swings by acting on different parts of the brain than originally thought, according to US research.

The research could lead to the development of new drugs which specifically target this chemical and could speed patients' recovery.

Scientists in San Francisco found that common anti-depressants which boost the brain chemical serotonin also have a major impact on another chemical only discovered in the past 10 to 15 years.

Anti-depressants have always been thought to work on a variety of brain chemicals, but the newer ones were targeted specifically at serotonin which is thought to play a big role in regulating mood.

The US scientists say they believe the new drugs - called selective serotonin re-uptake inhibitor (SSRIs) - can affect another type of brain chemical called a neurosteroid which may improve severe mood swings.

Writing in this week's Proceedings of the National Academy of Sciences, the researchers found that Prozac, Paxil and Zoloft greatly increased the synthesis of a key neurosteroid by up to 30 times.

They believe this is because they improve the functioning of an enzyme involved in synthesising the neurosteroid.

Dr Synthia Mellon, a senior author of the research, said: "Each of these three serotonin reuptake inhibitors, or SSRI's, shows a dramatic positive effect on the levels of allopregnanolone, a steroid made in the brain, which most likely modulates mood and plays a role in heightened anxiety and depression found in severe premenstrual disorders and other conditions."

She added: "The study points to the likelihood that SSRIs control mood by more than the one pathway that has received most of our attention, and it suggests that the steroids synthesized in the human brain may play a strong physiological role in regulating anxiety and depression."

Premenstrual tension

Other research has shown that low levels of neurosteroids are associated with depressive disorders such as premenstrual tension and that SSRIs can boost these and relieve symptoms.

The new study shows specifically how the SSRIs work on the neurosteroid allopreganolone.

The scientists used cloned DNA of enzymes involved in synthesising allopreganolone from rat and human tissue.

They found that SSRIs affected the brain chemical in a different way to how they boosted serotonin - by increasing the number and length of time apertures in the neurons' membranes remained open.

They also tested another type of anti-depressant and found it had no effect on allopreganolone.

Dr Cosmo Hallstrom, a UK specialist in depressive disorders, said the research was unlikely to be a breakthrough, but appeared to provide "another piece in the jigsaw" of how depression could be treated.

He added that it was clear that SSRIs did not just work on serotonin.

"Brain chemicals all interact with each other. You have to assume there is a knock-on effect on other parts of the nervous system. Depression cannot just be due to serotonin levels," he stated.

"If the depression is caused by neurosteroid deficiency, this finding could mean that new therapeutic avenues are opened which could speed up patients' recovery.